Hyperosmolar hyperglycaemic state as a stroke cause or stroke mimic: an illustrative case and review of literature

Discussion

HHS is an acute metabolic complication of type 2 diabetes, defined as marked hyperglycaemia resulting in serum osmolality >320 mOsm/kg without ketosis. Relative insulin deficiency and subsequent increase in counter-regulatory hormones leads to increased gluconeogenesis and glycogenolysis, and reduced uptake of glucose by peripheral tissues. Resulting severe hyperglycaemia leads to osmotic diuresis and profound dehydration.² HHS symptoms may develop insidiously over several days, notably polydipsia, polyuria, lethargy and altered mental state.^3,4 Common triggers are inadequate insulin therapy and illness such as infection, cerebrovascular disease and myocardial infarction.² Timely correction of hyperosmolality, hyperglycaemia and electrolyte abnormality is key to survival.² Without prompt treatment, HHS can lead to complications such as cerebral oedema, electrolyte derangement, myocardial infarction, stroke, seizures and central pontine myelinolysis.²

Despite neurological dysfunction being an established manifestation of HHS, there is limited research on the spectrum of neurological dysfunction. The most common presenting symptom is altered sensorium.⁵ Symptoms can range from lethargy to confusion and coma, with a demonstrated linear relationship between serum osmolality and obtundity.³ Others may present with focal neurology including hemianopia, hemiparesis, and focal or generalised seizures.^3,4 A retrospective case series investigating the variation in neurological complications of HHS had shown that coma was the most common presentation, followed by seizures and hemichorea-hemiballismus.⁶

The two previous case reports of HHS mimicking stroke feature transient neurological dysfunction with transient abnormal MRI findings (Table 1).^7,8 The first one described a 55-year-old man presenting with right homonymous hemianopia in the context of HHS.⁷ MRI of the brain revealed a subcortical lesion in left occipital lobe. However, both symptoms and MRI findings resolved on correction of HHS. Similarly, another report described an 67-year-old woman presenting with left middle cerebral artery syndrome.⁸ Investigations revealed severe hyperglycaemia. She was managed for HHS and received thrombolysis. MRI / magnetic resonance angiography / magnetic resonance perfusion at 6 hours showed a small abnormal area in the left posterior temporal lobe but no evidence of large vessel occlusion. Treatment of HHS led to resolution of all neurological symptoms within 24 hours of admission. Subsequent MRI at day 5 revealed no evidence of stroke or other condition consistent with her clinical presentation.It is theorised that either hyperosmolality and hyperviscosity result in hypoxic-ischaemic injury or ‘release’ of free radicals and the electroencephalography and the MRI findings are the result of reduced energy demand from inactive brain tissue.^7,8 This, in turn, leads to reduced perfusion rather than tissue at risk of infarction. However, a mechanism by which HHS causes metabolic change in such tissue is not known.⁸

Where neurological symptoms predominate, the diagnosis of HHS can be difficult to differentiate clinically from stroke.⁵ Importantly, our case highlights that the diagnoses are not mutually exclusive. Early studies around HSS and seizures often attributed patients with focal neurological deficits to Todd's paresis.⁸ However, at post-mortem, some of these patients had evidence of cerebral ischaemia.⁹ Those with HHS are at an increased risk of stroke due to the presence of diabetes and the acute prothrombotic state created by HHS.^10,11 Therefore, lateralising or deteriorating neurology should not always be attributed to HHS but should prompt consideration of concurrent cerebral ischaemia, particularly if the deficits develop after initiating treatment for HHS. This will enable successful management of both pathologies, particularly for time sensitive interventions such as thrombolysis and thrombectomy. In cases similar to our patient, further urgent imaging (such as CT angiography or MRI of the brain) will help guide whether reperfusion therapy is required, since such intervention should not be taken lightly in view of the bleeding risk associated with hyperglycaemia.¹²

Furthermore, our case demonstrates the confounding relationship between HHS and stroke through the ability of HHS to accentuate stroke symptoms ie a minor stroke resulted in significant neurological deficit out of keeping with the size of infarct. Subsequent treatment of HHS then rapidly improved neurological function.